(Revised Abstract) DESCRIPTION (provided by applicant): Opioid receptors are over-expressed by a variety of human and animal tumors. Markers for in vivo characterization of tumors expressing opioid receptors may have value as diagnostic aids, and would present opportunities for novel studies of the roles played by opioids in neoplasia. Little attention has focused on this arena despite the fact that opioid receptor antagonists are in clinical trials as antitumor agents, and widely prescribed opioid receptor agonists, such as morphine, may be tumor promoters. Our goal is to develop and validate imaging radioligands and mouse tumor models for in vivo studies of opioid receptors on breast and lung cancers in order to provide a foundation for future imaging studies of opioid receptor involvement in human cancers. Our emphasis will be upon radioligands labeled with 1-123, Tc-99m and In-111 for SPECT / microSPECT scanning. Further, we plan to determine the frequency and extent of expression of opioid receptors in human breast cancers by in vitro screening of biopsy samples and associated normal breast tissues, and to ascertain correlations of opioid receptor expression with a limited panel of tumor markers, including steroid hormone receptors. Specifically, we propose: (1) to design, synthesize and chemically characterize novel opioid receptor ligands labeled with SPECT imaging radionuclides; (2) to determine radioligand affinity, selectivity and specificity for opioid receptor types in vitro; (3) to characterize in vivo radioligand binding to opioid receptors in normal and tumor bearing rodents; (4) to evaluate radioligand pharmacokinetics and pharmacology in mice by microSPECT, and to use microSPECT and microCT imaging to investigate the effects of opioid receptor agonists and antagonists on MCF-7 mammary tumor xenograft growth in nude mice; and (5) to establish the frequency and extent of opioid receptor expression in human breast cancer biopsy specimens.